The Effect of Progression from Impaired Glucose Tolerance to Diabetes on Cardiovascular Risk Factors and its Amelioration by Lifestyle and Metformin Intervention: The Diabetes Prevention Program Randomized Trial

Abstract

Objective: Although subjects with diabetes have increased risk for cardiovascular disease (CVD), the evolution of this increased risk as prediabetic individuals progress to diabetes is not understood. This study examines the longitudinal relationship between selected CVD risk factors (blood pressure, triglyceride, HDL and LDL cholesterol and LDL peak particle density – [PPD]) and glycemia in the three treatment groups of the Diabetes Prevention Program.

Research Design and Methods: 3234 participants with IGT were followed for a mean of 3.2 years after randomization to intensive lifestyle intervention (ILS), metformin (MET) or placebo. Using repeated measures models, adjusted mean levels of risk factors were estimated for an annual change in glycemic status. Tests were also conducted to assess the risk factor trends with improvement or worsening of glycemic status.

Results: CVD risk factors values and changes from baseline became more unfavorable as glucose tolerance status deteriorated, but improved with reversion to NGT especially in the ILS intervention group (trend test p<0.001 for all risk factors except for LDL PPD (p=0.02) in ILS and HDL-C (p=0.02) in placebo). Although there were few significant differences in the transition from IGT to diabetes, there were strong relationships between risk factors and continuous measures of glycemia.

Conclusions: Progression from IGT to diabetes is associated with mild deterioration whereas reversion to NGT is associated with improvement in risk factors. Early intervention with ILS but less so with MET in participants at high risk for diabetes improves the cardiovascular risk and glucose tolerance profile simultaneously.